Trial reportHypertension (Dallas, Tex. : 1979)2012
Clinical significance of incident hypokalemia and hyperkalemia in treated hypertensive patients in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.
Trial report in Hypertension (Dallas, Tex. : 1979), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Dyskalemia risk associated with fixed-dose anti-hypertensive medication combinations.Journal of human hypertension · 2022Pooled it
- The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019).Hypertension research : official journal of the Japanese Society of Hypertension · 2019Guideline
- Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry.The pharmacogenomics journal · 2019Pooled it
- Comparative antiplatelet effects of chlorthalidone and hydrochlorothiazide.Journal of clinical hypertension (Greenwich, Conn.) · 2022Trial
- The Japanese Society of Hypertension Guidelines for the management of elevated blood pressure and hypertension 2025 (JSH2025).Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- The Impact of Potassium Dynamics on Cardiomyocyte Beating in Hemodialysis Treatment.Journal of clinical medicine · 2024Article
- Incidence rate of hypokalemic and its associated factors for patients undergoing noncardiac surgery: a retrospective analysis.Gland surgery · 2023Article
- Association between hyperkalemia, RAASi non-adherence and outcomes in chronic kidney disease.Journal of nephrology · 2022Observational
- Possible Advantages Deriving from Patiromer Use in Hypertensive Patients Made Hyperkalemic by Renin-Angiotensin-Aldosterone Blocking Agents.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2021Review
- Antihypertensive Prescribing for Uncomplicated, Incident Hypertension: Opportunities for Cost Savings.CJC open · 2021Article
- Management of hyperkalemia during treatment with mineralocorticoid receptor blockers: findings from esaxerenone.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Review
- Immediate and Delayed Response of Simulated Human Atrial Myocytes to Clinically-Relevant Hypokalemia.Frontiers in physiology · 2021Article
- Impact of plasma potassium normalization on short-term mortality in patients with hypertension and hypokalemia or low normal potassium.BMC cardiovascular disorders · 2020Observational
- Effects of fast-track anesthesia on miR-1 and neuropeptides in serum of patients undergoing cardiac surgery.Experimental and therapeutic medicine · 2020Article
- Antihypertensive therapy and sudden cardiac death, should we expect the unexpected?Journal of human hypertension · 2020Review
- A review of the prescribing trend of thiazide-type and thiazide-like diuretics in hypertension: A UK perspective.British journal of clinical pharmacology · 2019Review
- Observational
- Race, Serum Potassium, and Associations With ESRD and Mortality.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2017Observational
- Serum Potassium, Mortality, and Kidney Outcomes in the Atherosclerosis Risk in Communities Study.Mayo Clinic proceedings · 2016Article
- Electrolyte disturbance with diuretics and ACEIs.Canadian family physician Medecin de famille canadien · 2016Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Concerns exist that diuretic-induced changes in serum potassium may have adverse effects in hypertensive patients. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a large practice-based clinical trial, made it possible to examine consequences of observed changes in potassium during care in conventional practice settings. Normokalemic participants randomized to chlorthalidone (C) versus amlodipine or lisinopril as a first-step drug were stratified by year-1 potassium. Postyear-1 outcomes among hypokalemics (potassium, <3.5 mmol/L) and hyperkalemics (potassium, >5.4 mmol/L) were compared with normokalemics (potassium, 3.5-5.4 mmol/L). Year-1 hypokalemia incidence was 6.8%; incidence in C (12.9%) differed from amlodipine (2.1%; P<0.001) and lisinopril (1.0%; P<0.01). Hyperkalemia incidence (2.0%) was greater in lisinopril (3.6%) than in C (1.2%; P<0.01) or amlodipine (1.9%; P<0.01). Coronary heart disease occurred in 8.1% with hypokalemia, 8.0% with normokalemia, and 11.1% with hyperkalemia. Overall, mortality was higher in hypokalemics than in normokalemics (Cox hazard ratio, 1.21 [95% CI, 1.02-1.44]) with statistically significant (interaction, P<0.01) disparity in hazard ratios for the 3 treatment arms (hazard ratios, C=1.21, amlodipine=1.60, lisinopril=3.82). Hyperkalemia was associated with increased risk of combined cardiovascular disease (hazard ratio, 1.58 [95% CI, 1.15-2.18]) without significant treatment interactions. In conventional practice settings, the uncommon appearance of hyperkalemia was associated with increased cardiovascular disease risk. Hypokalemia was associated with increased mortality; however, the statistically significant heterogeneity in hazard ratios across treatment groups strongly suggests that the observed increase in mortality is unrelated to the specific effects of C. Thus, for most patients, concerns about potassium levels should not influence the clinician's decision about initiating hypertension treatment with low-moderate doses of thiazide diuretics (12.5-25.0 mg of C).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.